Transcriptional pattern enriched for synaptic signaling is associated with shorter survival of patients with high-grade serous ovarian cancer
Guardado en:
| Publicado en: | eLife vol. 13 (2025) |
|---|---|
| Autor principal: | |
| Otros Autores: | , , , , , , , , , , |
| Publicado: |
eLife Sciences Publications Ltd.
|
| Materias: | |
| Acceso en línea: | Citation/Abstract Full Text + Graphics Full Text - PDF |
| Etiquetas: |
Sin Etiquetas, Sea el primero en etiquetar este registro!
|
MARC
| LEADER | 00000nab a2200000uu 4500 | ||
|---|---|---|---|
| 001 | 3204558717 | ||
| 003 | UK-CbPIL | ||
| 022 | |a 2050-084X | ||
| 024 | 7 | |a 10.7554/eLife.101369 |2 doi | |
| 035 | |a 3204558717 | ||
| 045 | 2 | |b d20250101 |b d20251231 | |
| 100 | 1 | |a Bhattacharya Arkajyoti |u https://ror.org/012p63287 Department of Medical Oncology, University Medical Center Groningen, University of Groningen Groningen Netherlands | |
| 245 | 1 | |a Transcriptional pattern enriched for synaptic signaling is associated with shorter survival of patients with high-grade serous ovarian cancer | |
| 260 | |b eLife Sciences Publications Ltd. |c 2025 | ||
| 513 | |a Journal Article | ||
| 520 | 3 | |a Bulk transcriptomic analyses of high-grade serous ovarian cancer (HGSOC) so far have not uncovered potential drug targets, possibly because subtle, disease-relevant transcriptional patterns are overshadowed by dominant, non-relevant ones. Our aim was to uncover disease-outcome-related patterns in HGSOC transcriptomes that may reveal novel drug targets. Using consensus-independent component analysis, we dissected 678 HGSOC transcriptomes of systemic therapy naïve patients—sourced from public repositories—into statistically independent transcriptional components (TCs). To enhance c-ICA’s robustness, we added 447 transcriptomes from non-serous histotypes, low-grade serous, and non-cancerous ovarian tissues. Cox regression and survival tree analysis were performed to determine the association between TC activity and overall survival (OS). Finally, we determined the activity of the OS-associated TCs in 11 publicly available spatially resolved ovarian cancer transcriptomes. We identified 374 TCs, capturing prominent and subtle transcriptional patterns linked to specific biological processes. Six TCs, age, and tumor stage stratified patients with HGSOC receiving platinum-based chemotherapy into ten distinct OS groups. Three TCs were linked to copy-number alterations affecting expression levels of genes involved in replication, apoptosis, proliferation, immune activity, and replication stress. Notably, the TC identifying patients with the shortest OS captured a novel transcriptional pattern linked to synaptic signaling, which was active in tumor regions within all spatially resolved transcriptomes. The association between a synaptic signaling-related TC and OS supports the emerging role of neurons and their axons as cancer hallmark-inducing constituents of the tumor microenvironment. These constituents might offer a novel drug target for patients with HGSOC. | |
| 653 | |a Ovarian cancer | ||
| 653 | |a Transcriptomes | ||
| 653 | |a Patients | ||
| 653 | |a Gene expression | ||
| 653 | |a Datasets | ||
| 653 | |a Replication | ||
| 653 | |a Apoptosis | ||
| 653 | |a Therapeutic targets | ||
| 653 | |a Transcription | ||
| 653 | |a Tumor microenvironment | ||
| 653 | |a Tumors | ||
| 653 | |a Genomes | ||
| 653 | |a Transcriptomics | ||
| 653 | |a Chemotherapy | ||
| 653 | |a Survival analysis | ||
| 700 | 1 | |a Stutvoet, Thijs S |u https://ror.org/012p63287 Department of Medical Oncology, University Medical Center Groningen, University of Groningen Groningen Netherlands | |
| 700 | 1 | |a Perla Mirela |u https://ror.org/012p63287 Department of Medical Oncology, University Medical Center Groningen, University of Groningen Groningen Netherlands | |
| 700 | 1 | |a Loipfinger Stefan |u https://ror.org/012p63287 Department of Medical Oncology, University Medical Center Groningen, University of Groningen Groningen Netherlands | |
| 700 | 1 | |a Jalving Mathilde |u https://ror.org/012p63287 Department of Medical Oncology, University Medical Center Groningen, University of Groningen Groningen Netherlands | |
| 700 | 1 | |a Reyners Anna KL |u https://ror.org/012p63287 Department of Medical Oncology, University Medical Center Groningen, University of Groningen Groningen Netherlands | |
| 700 | 1 | |a Vermeer, Paola D |u https://ror.org/00sfn8y78 Cancer Biology and Immunotherapies Group, Sanford Research Sioux Falls United States | |
| 700 | 1 | |a Drapkin Ronny |u https://ror.org/00b30xv10 Penn Ovarian Cancer Research Center and Basser Center for BRCA, University of Pennsylvania, Perelman School of Medicine Philadelphia United States | |
| 700 | 1 | |a de Bruyn Marco |u https://ror.org/012p63287 Department of Obstetrics and Gynecology, University Medical Center Groningen, University of Groningen Groningen Netherlands | |
| 700 | 1 | |a de Vries Elisabeth GE |u https://ror.org/012p63287 Department of Medical Oncology, University Medical Center Groningen, University of Groningen Groningen Netherlands | |
| 700 | 1 | |a de, Jong Steven |u https://ror.org/012p63287 Department of Medical Oncology, University Medical Center Groningen, University of Groningen Groningen Netherlands | |
| 700 | 1 | |a Fehrmann, Rudolf SN |u https://ror.org/012p63287 Department of Medical Oncology, University Medical Center Groningen, University of Groningen Groningen Netherlands | |
| 773 | 0 | |t eLife |g vol. 13 (2025) | |
| 786 | 0 | |d ProQuest |t Science Database | |
| 856 | 4 | 1 | |3 Citation/Abstract |u https://www.proquest.com/docview/3204558717/abstract/embedded/7BTGNMKEMPT1V9Z2?source=fedsrch |
| 856 | 4 | 0 | |3 Full Text + Graphics |u https://www.proquest.com/docview/3204558717/fulltextwithgraphics/embedded/7BTGNMKEMPT1V9Z2?source=fedsrch |
| 856 | 4 | 0 | |3 Full Text - PDF |u https://www.proquest.com/docview/3204558717/fulltextPDF/embedded/7BTGNMKEMPT1V9Z2?source=fedsrch |